Effects of zinc deficiency and supplementation on plasma leptin levels in rats

The effects of zinc deficiency and supplementation on plasma leptin levels were studied in Sprague-Dawley rats. After 6 wk on a zinc-deficient diet containing 0.65 ppm Zn/g, the mean body weight was significantly lower than that of normal or zinc-supplemented rats, which showed no difference among them. The plasma leptin and zinc levels were lowest in zinc-deficient animals and highest in those that received a normal diet and daily intraperitioneal injections of 3 mg Zn/kg. These results indicate that zinc deficiency leads to a significant inhibition in plasma leptin levels, whereas zinc supplementation significantly increases plasma leptin.     

Daily zinc supplementation effect on zinc deficiency in rats during prolonged restriction of motor activity

The objective of this investigation was to evaluate the effect of 47 mg zinc supplementation on deficiency of zinc in rats during 98 d of restriction of motor activity (hypokinesia), which appeared by higher plasma zinc concentration. One Hundred 13-week-old Sprague-Dawley male rats weighing 360–390 g were used to perform the studies: They were equally divided into four groups: 1. Unsupplemented control animals (UCA); 2. Unsupplemented hypokinetic animals (UHA); 3. Supplemented control animals (SCA); and 4. Supplemented hypokinetic animals (SHA). For the simulation of the effect of hypokinesia (HK), the UHA and SHA were kept in small individual cages made of wood, which restricted their movements in all directions without hindering food and water intake. The SCA and SHA received daily with their food an additional amount of zinc. Before and during the experimental period of 98 d, plasma, urinary and fecal zinc, balance of zinc, food intake, and body weight were determined at different intervals. In the SHA and UHA, the concentration of zinc in plasma, and the elimination of zinc in urine and feces increased significantly when compared with the SCA and UCA, whereas the balance of zinc was negative. The body weight and food intake decreased significantly in the SHA and UHA when compared with the SCA and UCA. The increased plasma concentration of zinc in both the SHA and UHA groups was in contrast to the observed hypozincnemia during prolonged immobilization as during prolonged hospitalization. This reaction suggests that there may be some other mechanisms that are affecting the process of control and regulation of zinc metabolism during prolonged HK. It was concluded that exposure to prolonged restriction of motor activity of rats induces significant increases in plasma concentration, fecal and urinary elimination of zinc in the presence of negative zinc balance and regardless the daily intake of large amounts of zinc with their food, leading to zinc deficiency.     

Changes in iron, calcium, magnesium, copper, and zinc levels in different tissues of riboflavin-deficient rats

To clarify the changes of mineral levels in different tissues of riboflavin-deficient rats, Wistar rats were separated into three groups. One group was fed a diet ad libitum that was deficient in riboflavin. The other two were fed either the complete diet that was weight-matched to the riboflavin-deficient group or fed a complete diet ad libitum. In riboflavin-deficient rats, the hemoglobin concentration and riboflavin contents of blood, liver, and kidney were significantly decreased, compared with weight-matched and ad libitum-fed controls. The mineral concentrations of tissues are summarized as follows: The iron (Fe) concentration in the heart, liver, and spleen was decreased in the riboflavin-deficient group compared with the other groups. Calcium (Ca) and magnesium (Mg) concentrations in tibia were decreased in the riboflavin-deficient group compared with the other two groups. Copper (Cu) concentration was increased in the heart and liver when the riboflavin-deficient group was compared with the other groups. Zinc (Zn) concentration was increased in tibia when the riboflavin-deficient group was compared with the other groups.     

Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia

In order to evaluate serum copper and zinc status in children with iron deficiency anemia (IDA), 60 children with IDA aged 1–14 yr and 64 healthy children as controls aged 1–14 yr were included the study. Serum copper levels were higher in children with IDA (189 ± 49 (Μg/dL) than those of controls (163 ± 37 Μg/dL) (p = 0.001). Serum zinc levels were lower in the patient group (109 ± 59 Μg/dL) than those of control subjects (135 ± 56 Μg/dL) (p = 0.017). In addition, there were statistically significant negative correlations between hematological parameters and serum copper levels in the patient group, but not in controls. No correlation between hematological parameters and serum zinc levels were found in both patient and control groups, except positive correlation between mean corpuscular volume (MCV) and serum zinc level in patients. It was concluded that at the time of managing children with IDA, zinc deficiency must be borne in mind and if necessary treatment should be initiated with zinc.     

Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia

In the present study, the serum and hair levels of zinc, selenium, and copper were determined in children with iron-deficiency anemia (IDA). A total of 52 anemic children aged 1–4 yr constituted the study group. Fortysix healthy children acted as controls. The copper and zinc levels were measured with an atomic absorption spectrophometer. Serum and hair selenium was determined by a spectroflourometric method. The serum zinc and selenium concentrations in the IDA group were found to be significantly lower and serum copper significantly higher than those in the controls (p<0.05). Lower iron, zinc, and selenium concentrations (p<0.001) but not copper were found in hair (p>0.05).     

Serum zinc, selenium, copper, and lead levels in women with second-trimester induced abortion resulting from neural tube defects

Neural tube defects are important causes of infant mortality and childhood morbidity. We investigated the relationship between zinc, selenium, copper, and lead concentrations and neural-tube-defect occurrence in women with a second-trimester termination due to fetal-neural-tube defects (NTDs) in this case-control study. Fourteen pregnant women whose pregnancies were terminated as a result of second-trimester ultrasonographic diagnosis of neural tube defects were recruited as cases. The control group (n=14) consisted of women who were selected among age-, gravidity-, and socio-economic-state (SES)-matched women who had a normal triple-screen and targeted ultrasound during the second trimester with documented normal fetal outcome. Zinc and copper determinations were made using flame atomic absorption spectrophotometer (AAS). Graphite furnace AAS was used for Pb, and Se levels were measured with hydride generation AAS. Cases had significantly low serum zinc and selenium levels (62.48±15.9 vs 102.6±23.7 and 55.16±11.3 vs 77.4±5.5, respectively, p<0.001). Serum Cu and whole-blood Pb levels were significantly high when compared to controls. There was a negative correlation between serum zinc and selenium levels, and serum copper levels (r=−425 and −0.443, p<0.05). Our results are consistent with some previous reports. The etiology of NTDs cannot be explained with one strict etiologic mechanism. On the contrary, an interaction among environmental, genetic, and nutritional factors such as trace elements and vitamins would explain these anomalies. If folic acid supplementation is given, additional Zn supplementation should be considered for the further decrease in the recurrence and occurrence of NTDs.     

Effect of zinc supplementation on the antioxidant,copper, and iron status of physically active adolescents

Puberty associated with intense physical activity results in oxidation stress. Zinc supplementation may benefit antioxidant capacity although it may also affect iron and copper status. This study evaluated the effect of zinc supplementation on antioxidant, zinc and copper status of physically active male football players (13 years ± 0.4 years), divided in two groups and studied during 12 weeks: Zn‐supplemented (Zn‐SUP, 22 mg Zn d^?1 as zinc gluconate, n = 21) and placebo (PLA, n = 26). At baseline, there was no significant difference in biochemical indices between the two groups. After treatment, plasma zinc and erythrocyte iron increased in both groups (p < 0.001); urinary zinc increased (p < 0.001) only in Zn‐SUP, and erythrocyte zinc decreased (p = 0.002) only in PLA. Plasma iron and copper decreased (p = 0.01 and p = 0.015, respectively) only in Zn‐SUP. Plasma ferric‐reducing ability and plasma conjugated dienes increased, and erythrocyte osmotic fragility decrease in both groups, although the latter two were significantly lower in Zn‐SUP compared to PLA (p < 0.01). In conclusion, our study indicates that the use of 22 mg d^?1 of supplemental zinc during 12 week in adolescent athletes did not affect growth, improved markers of antioxidant status but reduced plasma iron and copper. Therefore, it appears that the use of zinc supplementation by healthy adolescent athletes benefits their antioxidant capacity but impairs copper and iron nutritional status. Copyright © 2009 John Wiley & Sons, Ltd.     

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite. An erratum to this article is available at .     

Seasonal changes of zinc, copper, and iron in gilthead sea bream (Sparus aurata) fed fortified diets

Four groups of gilthead sea bream (Sparus aurata) were fed diets with additional metal contents: a basal diet (diet A) contained Zn at 60.9 ± 1.9 mg/kg diet, Cu at 3.9 ± 0.9 mg/kg diet, and Fe at 138.3 ± 6.8 mg/kg diet; the other diets were supplemented with copper (20 mg/kg, diet B), iron (100 mg/kg, diet C), or zinc (300 mg/kg, diet D). Two consecutive year-classes (0⁺ and 1⁺ age fish) from the same parent stock were examined. Several fish tissues were analyzed for metal contents in five different periods of each year in order to determine (1) the sensitivity of certain tissues as indicators of trace element metabolism and (2) possible seasonal variations. Growth data were similar for gilthead sea bream fed the basal diet and the metal-fortified diets. Mineral concentrations in tissues were found to be little affected by the dietary supplementation of trace elements, suggesting an efficient homeostatic control of these three metal concentrations. Tissues involved in metal metabolism (e.g., liver, kidney, gills) presented greater variations between minimum and maximum values with respect to other tissues (e.g., brain, muscle, eye). Seasonal variations were observed during the 2 yr of this study and were especially evident for zinc and copper concentrations in the liver. The overall pattern of metal variations showed a decreasing trend during the 2 yr. Results from this study indicate that (1) trace element concentrations in fish tissues vary with age and life cycle and (2) trace element requirements may vary in function of age and life cycle.     

Effects of rutin supplementation on antioxidant status and iron,copper, and zinc contents in mouse liver and brain

The effect of rutin on total antioxidant status as well as on trace elements such as iron, copper, and zinc in mouse liver and brain were studied. Mice were administrated with 0.75 g/kg or 2.25 g/kg P. O. of rutin for 30 d consecutively. Following the treatment, the activity of total antioxidant status, catalase, Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, zinc, copper, and iron were measured in mouse liver and brain. The results showed that rutin significantly increased the antioxidant status and Mn-superoxide dismutase activities in mouse liver, but it had no effect on these variables in the brain. Treatment with a higher concentration of rutin significantly decreased catalase activity and iron, zinc, and copper contents in mouse liver; it also resulted in a slower weight gain for the first 20 d. These results indicate that rutin taken in proper amount can effectively improve antioxidant status, whereas at an increased dosage, it may cause trace element (such as iron, zinc, and copper) deficiencies and a decrease in the activities of related metal-containing enzymes.     

Associations among plasma selenium,zinc, copper,and iron concentrations and immunoregulatory cytokine levels in patients with cutaneous leishmaniasis

Plasma essential trace elements, selenium, copper, zinc, and iron concentrations and the levels of immunoregulatory cytokines, interleukin-1β (IL-1β), interleukin-2 receptor (IL-2r), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were evaluated in patients with cutaneous leishmaniasis (CL) to investigate a possible role of these cytokines on selenium, zinc, copper, and iron homeostasis in CL patients. Plasma albumin levels were measured as an index of nutritional status. Plasma selenium, zinc, and iron concentrations, and IL-2r levels were significantly lower, and copper concentrations and IL-1β, IL-8, IL-6 and TNF-α levels were significantly higher in patients with CL than those of healthy controls. There was no significant difference in plasma albumin levels between two groups. There were positive important correlations between plasma selenium and IL-2r, copper and IL-6, and copper and IL-1β, and negative correlations between selenium and IL-8, iron and TNF-α, and zinc and IL-1β contents in patients with CL. Our results showed that plasma trace element contents change in patients with CL. These changes may not be a result of a specific deficiency from dietary inadequacies or imbalances, but, probably, a result of a part of the defense strategies of an organism that is regulated by immunoregulatory cytokines.     

Chronological changes in tissue copper, zinc and iron in the toxic milk mouse and effects of copper loading

The toxic milk (tx) mouse is a rodent model for Wilson disease, an inherited disorder of copper overload. Here we assessed the effect of copper accumulation in the tx mouse on zinc and iron metabolism. Copper, zinc and iron concentrations were determined in the liver, kidney, spleen and brain of control and copper-loaded animals by atomic absorption spectroscopy. Copper concentration increased dramatically in the liver, and was also significantly higher in the spleen, kidney and brain of control tx mice in the first few months of life compared with normal DL mice. Hepatic zinc was increased with age in the tx mouse, but zinc concentrations in the other organs were normal. Liver and kidney iron concentrations were significantly lower at birth in tx mice, but increased quickly to be comparable with control mice by 2 months of age. Iron concentration in the spleen was significantly higher in tx mice, but was lower in 5 day old tx pups. Copper-loading studies showed that normal DL mice ingesting 300 mg/l copper in their diet for 3 months maintained normal liver, kidney and brain copper, zinc and iron levels. Copper-loading of tx mice did not increase the already high liver copper concentrations, but spleen and brain copper concentrations were increased. Despite a significant elevation of copper in the brain of the copper-loaded tx mice no behavioural changes were observed. The livers of copper-loaded tx mice had a lower zinc concentration than control tx mice, whilst the kidney had double the concentration of iron suggesting that there was increased erythrocyte hemolysis in the copper-loaded mutants.     

Hair and serum calcium, iron, copper, and zinc levels during normal pregnancy at three trimesters

The hair and serum levels of calcium, iron, copper, and zinc levels were measured in a group of 70 healthy pregnant women and in 66 age-matched healthy controls living in the Tianjin city of the People’s Republic of China. The study subjects were classified into three subgroups according to gestational age. The hair concentrations were measured by X-ray fluorescence spectrometry, whereas those in sera were established by atomic absorption spectrometry. The hair concentrations of Ca, Fe, Cu, and Zn in the three groups of gravida were lower or significantly lower than those in controls. In sera, the differences did not show statistical significance in most cases. A deficiency of calcium was observed in subjects in the last trimester of gestation. This reinforces the importance of supplementation with calcium during pregnancy.     

Selenium, iron, copper, and zinc levels and copper-to-zinc ratios in serum of patients at different stages of viral hepatic diseases

Viral hepatic diseases, especially those induced by the hepatitis B virus, can progress into more serious pathological outcomes and eventually to hepatocellular carcinoma. A growing body of evidence indicates that many trace elements play important roles in a number of carcinogenic processes that proceed through various mechanisms. To examine the status of trace elements during the development of hepatic carcinoma, we determined the selenium, iron, copper, and zinc levels and copper-to-zinc ratios in the serum of patients at different stages of viral hepatic disease. We observed significant changes in the selenium, iron copper, and zinc levels in the serum of patients having hepatocellular carcinoma, relative to those of healthy controls (p<0.05). The mean serum copper level in patients with hepatocellular carcinoma was significantly higher than that of the control group. In contrast, the mean selenium, iron, and zinc levels in patients having hepatocellular carcinoma were significantly lower than those of the control group. In addition, the mean zinc level in the serum of patients with hepatic cirrhosis was significantly lower than that of the control group (p<0.05). Moreover, we found markedly elevated Cu: Zn ratios (p<0.05) in patients having hepatic cirrhosis or hepatocellular carcinoma. Our findings imply that the levels of some trace elements, such as selenium, iron, copper, and zinc, and Cu:Zn ratios, might serve as biomarkers for the increased severity of viral hepatic damage.     

The relationship between zinc and copper status and lipid levels in African-Americans

Studies examining the role of zinc and copper nutriture as risk factors for cardiovascular disease in European Americans have produced conflicting results. This study assessed the associations between zinc and copper status and serum lipid levels in an adult African-American community. A cross-sectional study was conducted on 600 individuals (233 males, 367 females) from 25 to 65 yr of age using a random sampling design in a small city in Alabama. Anthropometric, dietary, and serum zinc, copper, and lipid measurements were made. The mean serum zinc and copper levels and dietary zinc intake were similar to that reported previously for European Americans. There were no significant associations between serum zinc, copper, or zinc/copper ratio and total serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or triglyceride levels. For males, there was a small but significant association between dietary zinc and the total cholesterol/HDL-C ratio (r=−0.17, p=0.03). Similarly, females taking either zinc supplements or a multivitamin including zinc had higher HDL-C values than nonsupplementing females. Further prospective studies of the relationship between zinc status and lipid levels in African Americans are needed to verify these results.     

Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia

A number of essential trace elements play a major role in various metabolic pathways. Selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential trace elements that have been studied in many diseases, including autoimmune, neurological, and psychiatric disorders. However, the findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied these elements in patients with a DSM-IV diagnosis of schizophrenia and compared them with sex- and age-matched healthy controls. Plasma Cu concentrations were significantly higher (p<0.01) and Mn and Fe concentrations were lower (p<0.05 and p<0.05, respectively) in schizophrenic patients than in controls. Se and Zn concentrations and protein levels did not differ between patients and healthy controls. These observations suggest that alterations in essential trace elements Mn, Cu, and Fe may play a role in the pathogenesis of schizophrenia. However, findings from trace element levels in schizophrenia show a variety of results that are difficult to interpret.     

Effects of iron,copper, zinc,calcium, and magnesium on human lymphocytes in culture

The effects of simultaneous changes of calcium, magnesium, iron, copper, and zinc concentrations were evaluated in normal human T and B lymphocytes, cultured in cation-depleted media. Optimal concentrations for thymidine incorporation (TI) in both cell populations were Fe and Zn 15 μM and Cu 5 μM; for t cells Ca 2 mM and Mg 4 mM; for B cells Ca 4 mM and Mg 6 mM. TI decreased with increasing molarity of cations and the decrease was particularly apparent with Cu. Minimal amounts of Ca and Mg (0.5 mM) were necessary for growth, even in presence of optimal concentrations of Fe, Cu, and Zn. Fe and Cu showed synergistic stimulatory effects at low concentrations and synergistic inhibitory effects at high concentrations. Antagonism between Fe and Zn, Cu and Zn, and Ca and Zn was also demonstrated. CD4/CD8 increased with PHA stimulation in presence of Zn, and decreased with ConA stimulation in presence of Zn or Fe. The results demonstrate: (1) the relationship and interdependence of Fe, Cu, and Zn concentrations in modulating the growth of normal lymphocytes; (2) the stimulatory effects of Fe on B cells and Zn on CD8 positive cells; (3) the inhibitory effect of Cu at concentrations lower than those of Fe and Zn; (4) the requirement of Ca and Mg in certain concentration and ratio for the action of the other cations; and (5) the Ca and Mg requirement for the growth of B cells higher than T cells.     

Selenium status,plasma zinc,copper, and magnesium in vegetarians

Plasma zinc (Zn), copper (Cu), and magnesium (Mg) concentrations, copper/zinc ratio, and selenium (Se) status were studied in 44 vegetarians (22 males and 22 females) and their age- and sex-matched nonvegetarians in the Bratislava region (Slovakia). Vegetarians had statistically significant lower levels of plasma Zn and Cu than nonvegetarians, which may be the result of lower bioavailability of Zn and Cu from this type of diet. No differences in plasma Mg levels were found between vegetarians and nonvegetarians. Se status, as expressed by plasma and erythrocyte concentrations and plasma and erythrocyte glutathione peroxidase activities (GPx), was significantly lower in vegetarians when compared to nonvegetarians. In the series as a whole, there were significantly higher correlations between plasma and erythrocyte Se concentrations and between plasma and erythrocyte GPx activities. Significant positive correlations were also found between plasma Se concentrations and erythrocyte GPx activities, and between erythrocyte Se concentrations and erythrocyte GPx activities. A vegetarian diet does not provide a sufficient supply of essential antioxidant trace elements, like Zn, Cu, and especially Se. Se supplementation should be recommended to this risk group of the population.     

Serum zinc and copper levels in southeastern Turkish children with giardiasis or amebiasis

Alterations of serum zinc (Zn) and copper (Cu) concentrations are commonly found in patients suffering from gastrointestinal infections and with hepatic, renal, cardiovascular, and malignant diseases. In this study, the serum Zn and Cu levels in 20 children with giardiasis and in 40 children with amebiasis were evaluated. The serum Zn levels showed a significant decrease when compared to controls (p<0.001). After metronidazole therapy, a significant increase in Zn levels was observed (p<0.001). There was no significant difference in serum Cu levels between patients and controls before therapy. Before therapy, the serum Cu/Zn ratio in children with either giardiasis or amebiasis was significantly higher than that of the control group. After therapy, the Cu/Zn ratio was found to be back to normal. There were no significant differences in serum Zn levels and Cu/Zn ratios between children with and without diarrhea and there was no significant difference in children with or without failure to thrive. We concluded that Zn deficiency and elevated Cu/Zn ratio could be acute-phase responses to parasitic infections in children with giardiasis or amebiasis and that a successful treatment of the primary disorder will lead to complete recovery. Further studies are in progress to confirm the benefit of Zn supplementation during the acute phase of the disease, particularly in zinc-deficient regions of the world, such as in the case of Turkey.     

The effect of various dietary zinc concentrations on the biological interactions of zinc,copper, and iron in rats

Three groups (14 rats each) were fed one of the following diets for 8 wks: a control purified basal diet containing 12 ppm zinc, 5 ppm copper, and 35 ppm iron; the basal diet with less than 2 ppm zinc; or the basal diet supplemented with 1000 ppm zinc. Rats fed the zinc-deficient diet had decreased weight gain, moderate polydipsia, and intermittent mild diarrhea. The zinc-supplemented rats had a cyclical pattern of food intake and weight loss from weeks 5 to 8. Tissue concentrations suggest that zinc and copper were not mutually antagonistic with chronic dietary imbalances. If tissue element concentrations reflected intestinal uptake, then competition and/or inhibition of intestinal uptake occurred between zinc and iron. The fluctuations in tissue element concentrations that occurred with increased duration of the study were at variance with previous studies of shorter time periods. The dietary proportions of zinc, copper, and iron appear to influence zinc, copper, and iron metabolism at the intestinal and cellular transport levels over a given period of time.